$1.4 million NIH grant to UB scientist to study effects of arsenic on cancer tumor production

Xuefeng Ren has received a $1.4 million grant from the National Institutes of Health to study how chronic arsenic exposure works in the body, research that could lead to new methods of prevention and treatment.

“By identifying the locations of arsenic-induced chromatin alterations, we hope to provide a completely new type of epigenetic biomarker for arsenic-associated cancers. This will allow us to identify people at high risk for developing these cancers.”

BUFFALO, N.Y. – University at Buffalo faculty member
Xuefeng Ren has received a $1.4 million grant from the National
Institutes of Health to investigate the mechanisms of arsenic
carcinogenesis — the process by which exposure to arsenic
transforms normal cells into cancer cells.

Chronic exposure to arsenic, a ubiquitous element widely
distributed in the natural environment, affects up to 100 million
people in 70 countries, including the United States. It can lead to
increased morbidity and mortality from both non-cancerous and
cancerous effects, including diabetes, peripheral neuropathy,
cardiovascular diseases and cancers of the bladder, lung, kidney
and skin.

Many environmental scientists are wrestling with ways to deal
with the problem at its most ubiquitous source: groundwater that is
naturally contaminated with inorganic arsenic compounds.

Ren and his team, however, will employ an integrated approach
that combines cell and molecular biology with epidemiology in order
to decipher how chronic arsenic exposure works in the body. This
could lead to new methods of prevention and treatment.

Ren, an assistant professor of epidemiology and environmental
health in the School of Public Health and Health Professions, says
that although the relationship between arsenic exposure and cancer
is well documented, the mechanisms by which arsenic participates in
the production of tumors are not clear.

He says researchers theorize that arsenic causes changes in the
epigenome, which is the record of chemical changes to the DNA and
histone proteins that affect both gene expression and
carcinogenesis.

“This study will examine the molecular mechanisms of MMA
(III) or monomethylarsenous acid, a substance composed of highly
toxic arsenic metabolites, in inducing or precipitating the
malignant transformation of human cells,” he says.

He explains that chromatin is the mass of genetic material in
the nucleus of a cell composed of DNA and proteins that condense to
form chromosomes.

“A unique aspect of this study is that it is expected to
identify the early and likely driving chromatin/epigenetic changes
responsible for aberrant gene expression in MMA (III)-induced cell
malignant transformation,” Ren says.

His long term goal, he says, is to define the effects and
consequences of chronic arsenic exposure on the epigenome, which
could allow targeted therapeutic interventions with
epigenetic-targeting drugs.

“Moreover,” he says, “by identifying the
locations of arsenic-induced chromatin alterations, we hope to
provide a completely new type of epigenetic biomarker for
arsenic-associated cancers. This will allow us to identify people
at high risk for developing these cancers.”

UB co-investigators with Ren on the study are Michael Buck,
assistant professor, Department of Biochemistry, School of Medicine
and Biomedical Sciences, and director of the UB Stem Cell
Sequencing/Epigenomics Center (WNYSTEM), and Daniel Gaile,
assistant professor, Department of Biostatistics, School of Public
Health and Health Professions.

Other significant contributors include Xiaojuan Guo and Hongmei
Wu of Wenzhou Medical University, China, and Allan H. Smith of the
University of California, Berkeley.

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